CTNI-77. Phase 1 study of tumor treating fields concurrent with 5 day hypofractionated stereotactic radiosurgery with concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma..

Abstract BACKGROUND Preclinical data suggest greater efficacy of radiotherapy when combined with Tumor Treating Fields (TTFs). Building upon our previous phase I trial of 5-fraction stereotactic radiosurgery (SRS), we sought to determine the safety of adding TTFs concurrent with 5-day SRS with concurrent and adjuvant Temozolomide (TMZ). METHODS Adult patients with newly diagnosed glioblastoma (GBM) were enrolled and treated with TTFs (on Day 1) and TMZ (75 mg/m2/day on Days 1-8) concurrent with hypofractionated SRS (35 Gy in 5 fractions starting on Day 2). TTFs were taken off each day during SRS. Adjuvant TMZ was not protocol defined and was per standard of care. Acute (within 1 month) and late (from 1 to 5 months) dose limiting toxicity (DLT) was defined as any treatment-related G3-5 adverse event (AE) (except reversible G3 hematologic), including device-related dermatologic AEs and brain necrosis/edema. Secondary endpoints included progression-free survival (PFS) per RANO and overall survival (OS). RESULTS From 2021 to 2024, twelve patients were enrolled. The median age was 71 years (range, 47-77 y). No patients had acute DLT. Late DLT occurred in 1 patient (G3 insomnia). The highest-level device-related dermatologic AEs were G1 in 7 patients, G2 in 5 patients. Late radiation necrosis occurred in 3 patients (all G1-2; none with G3-5). Median PFS was 10.5 months (95% CI: 10.3-10.6), median OS was 15.1 months (95% CI: 14.9-15.4). OS was 15.2 months if MGMT positive for hypermethylation (n=2 patients),15.0 months if MGMT negative (n=10 patients). CONCLUSION TTFs concurrent with 5-day hypofractionated SRS and TMZ were well tolerated, with no G3+ late radiation necrosis nor G3+ device-related dermatologic toxicity.